The importance of neuronal growth factors in the ovary.

The neurotrophin family consists of nerve growth factor (NGF), neurotrophin 3 (NT3) and neurotrophin 4/5 (NT4/5), in addition to brain-derived neurotrophic factor (BDNF) and the neuronal growth factors, glial cell line-derived neurotrophic factor (GDNF) and vasointestinal peptide (VIP). Although there are a few literature reviews, mainly of animal studies, on the importance of neurotrophins in the ovary, we aimed to provide a complete review of neurotrophins as well as neuronal growth factors and their important roles in normal and pathological processes in the ovary. Follicular assembly is probably stimulated by complementary effects of NGF, NT4/5 and BDNF and their receptors. The neurotrophins, GDNF and VIP and their receptors have all been identified in preantral and antral follicles of mammalian species, including humans. Transgenic mice with mutations in the genes encoding for Ngf, Nt4/5 and Bdnf and their tropomyosin-related kinase ß receptor showed a reduction in preantral follicles and an abnormal ovarian morphology, whereas NGF, NT3, GDNF and VIP increased the in vitro activation of primordial follicles in rats and goats. Additionally, NGF, NT3 and GDNF promoted follicular cell proliferation; NGF, BDNF and VIP were shown to be involved in ovulation; VIP inhibited follicular apoptosis; NT4/5, BDNF and GDNF promoted oocyte maturation and NGF, NT3 and VIP stimulated steroidogenesis. NGF may also exert a stimulatory effect in ovarian cancer and polycystic ovarian syndrome (PCOS). Low levels of NGF and BDNF in follicular fluid may be associated with diminished ovarian reserve and high levels with endometriosis. More knowledge of the roles of neuronal growth factors in the ovary has important implications for the development of new therapeutic drugs (such as anti-NGF agents) for ovarian cancer and PCOS as well as various infertility problems, warranting further research.

NETs, infections, and antimicrobials: a complex interplay.

In response to a range of stimuli, neutrophils produce web-like structures known as neutrophil extracellular traps (NETs). The benefits of NETs in pathogen control are commonly offset by excessive release as part of a pro-inflammatory response, as shown in several disorders. The discovery of potential drugs that regulate NET release has helped to enhance our understanding of the role of NETs in immunological protection, inflammatory diseases, and autoimmune disorders. Emerging evidence has indicated that antimicrobials play an immunomodulatory role by influencing the levels of circulating NETs. Herein, we address NETosis in several disorders and detail the mechanisms of NET-mediated damage in infections. We also aim to evaluate recent evidence on the effects of antimicrobials on NET levels. Relevant keywords were searched in PubMed. Studies were evaluated for their relevance, and a narrative review was written accordingly. Several antibiotics, including beta-lactams and cephalosporins, alter NET formation and degradation in a protective manner, resulting in minimal host organ damage. Additionally, some studies have highlighted the immunomodulatory effects of antivirals and antifungals on NET. Further studies are needed to fully understand the clinical implications of NET-antimicrobial interactions and their underlying mechanisms.